Hypercortisolemia and increased levels of hyperphosphorylated tau proteins in cerebrospinal fluid (CSF) are common features with pathogenic relevance in Alzheimer;s disease (AD). Experimental studies point to an influence of cortisol on Abeta and tau pathology in AD. Association of both parameters have not yet been described in a sample of AD patients. In the present study, serum levels of cortisol were determined in 26 patients with mild AD dementia and 20 age-matched healthy elderly controls by ELISA. In addition, we measured in AD patients CSF levels of cortisol, total tau (T-tau), tau phosphorylated at threonine 181 (P-tau 181), tau protein phosphorylated at threonine 231 (P-tau 231) and beta-Amyloid (Abeta) 1-42 and determined T-tau/Abeta 1-42 ratios in CSF. We found in AD patients significantly increased cortisol serum levels (551.4 +/- 146.1 nmol/l; P = 0.002) as compared to healthy controls (435.3 +/- 83.9 nmol/l). In AD patients, cortisol serum levels were significantly inversely correlated with T-tau (r = -0.496; P = 0.01), P-tau 181 (r = -0.558; P = 0.003) and P-tau 231 (-0.500; P = 0.009) protein levels and T-tau/Abeta 1-42 ratios (r = -0.450; P = 0.021) in CSF. In addition, cortisol serum levels showed a trend of positive correlation with Abeta 1-42 CSF levels (r = 0.386; P = 0.052). However, no significant correlations of cortisol serum with CSF levels as well as cortisol CSF levels with CSF biomarkers could be detected in AD patients. In conclusion, our results show that increased cortisol serum but not CSF levels are associated with minor signs of AD pathology in CSF, indicating a putative neuroprotective effect of moderately elevated cortisol serum levels in patients with mild AD dementia.